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clinical review
Coronary Computed Tomography Angiography
for the Diagnosis of Coronary Artery Disease
Troy LaBounty, MD, Mauro Moscucci, MD, and Ella A. Kazerooni, MD, MS
Abstract
• Objective: To review the current application of coronary computed tomography angiography (CCTA) in
the diagnosis of coronary artery disease (CAD).
• Methods: Qualitative review of the literature.
• Results: CCTA has emerged as a potential noninvasive alternative to both existing noninvasive tests
for CAD in some patients and invasive coronary
angiography (ICA) in other patients. There have been
a large number of small, single-center studies comparing CCTA with ICA for the diagnosis of significant
CAD that have reported excellent sensitivity, specificity, and negative predictive value in patient populations with a high prevalence of CAD. These studies
often exclude segments or patients who do not have
complete visualization of all coronary segments and
it can be particularly challenging in patients with
significant coronary artery calcification, stent placement, or coronary artery bypass grafts. A few small
studies have evaluated the use of CCTA in the diagnosis of chest pain in the emergency department.
• Conclusion: To date, there are little data on the role
of CCTA in comparison with other noninvasive tests
for the diagnosis of CAD, including nuclear perfusion
imaging and stress echocardiography. Given the
ac­curacy of CCTA, it may be useful as a strategy
to avoid ICA. The high negative predictive value of
CCTA suggests great promise in the assessment of
low- to moderate-risk patients with acute chest pain,
with the potential for rapid patient triage and lower
health care costs.
C
ardiovascular disease is the leading cause of death in
the United States. Over 13 million American adults
have coronary heart disease, for which invasive
coronary angiography (ICA) represents the gold standard for
the diagnosis. More than 1.4 million inpatient coronary angiograms and 664,000 percutaneous coronary interventions
(PCIs) were performed in the United States in 2003 [1]. ICA is
associated with a major procedure-related complication rate
in 1.7% of patients and a procedure-related mortality rate of
0.1% [2]. Given these risks, the expense, and postprocedure
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recovery time associated with ICA, there is great interest
in the noninvasive diagnosis of coronary artery disease
(CAD) using coronary computed tomography angiography
(CCTA). Like ICA, this new technique visualizes the artery
lumen, but unlike ICA, CCTA also visualizes the vessel wall
and can characterize plaque area, volume, and remodeling
and can discriminate between calcified and soft plaques
(Figure 1 and Figure 2) similar to intravascular ultrasound
(IVUS) [3].
There are now established criteria for the appropriate
use of CCTA (Table 1) [4], and CCTA is deemed reasonable
(Class IIa recommendation) in the evaluation of suspected
obstructive CAD in symptomatic patients. Other uses of
CCTA include the detection and mapping of coronary artery
anomalies (Class IIa recommendation) [5], evaluation of
congenital heart disease, preprocedure anatomic mapping,
and evaluation of cardiac masses; however, these are beyond
the scope of this review.
The detection of CAD on multidetector-row computed
tomography (MDCT) has also been shown to have prognostic implications. In 100 patients who underwent MDCT for
suspected CAD, the 1-year incidence of cardiac death, acute
coronary syndrome (ACS), or revascularization was 30%
in patients with any CAD versus 0% in those with normal
coronary arteries [6]. A study of 1138 patients who underwent MDCT and a mean follow-up of 15 months found that
patients with absent or mild CAD had a 99.7% survival rate,
whereas patients with moderate or severe CAD had an 85%
survival rate [7].
Recent data suggest that optimal medical management
in patients with stable angina and significant ischemic CAD
with or without PCI may result in equivalent rates of death,
myocardial infarction, or other cardiovascular events [8].
Given the potential shift from PCI to medical management
alone in some patients, there may be a greater role for a
noninvasive test such as CCTA to diagnose CAD, with potentially less use of diagnostic ICA.
From the Department of Internal Medicine, Division of Cardiology (Drs.
LaBounty and Moscucci), and Department of Radiology, Division of Cardiothoracic Radiology (Dr. Kazerooni), University of Michigan, Ann Arbor, MI.
Vol. 14, No. 8 August 2007 JCOM 447
coronary ct angiography
A
A
B
B
Figure 1. Both invasive coronary angiography (A) and coronary computed tomography angiography (CCTA, B) demonstrate a lesion in the right coronary artery (large arrows), with
CCTA demonstrating the plaque composition to be mixed,
both calcified (small arrow) and noncalcified.
Figure 2. Both invasive coronary angiography (A) and coronary
computed tomography angiography (CCTA, B) demonstrate
a lesion in the left anterior descending artery (large arrows).
There is extensive calcification distally on CCTA (small arrow).
General Technical Principles
CCTA requires the use of the most recent generations of
multidetector computed tomography (CT) scanners that are
capable of providing a dataset with both high spatial and
temporal resolution that is reconstructed in synchrony to
simultaneously collected electrocardiogram (ECG) data, essentially suspending cardiac motion. Patients with irregular
rhythms cannot undergo CCTA, as ECG and CT data cannot
be aligned currently. Helical scanning requires the continuous movement of both the CT gantry and the CT scanning
table. With multidetector CT scanners, multiple rows of data
are obtained with each 360-degree rotation of the CT gantry.
Modern commercially available scanners have detector arrays with up to 64 detector rows, and gantry rotation speeds
of under 500 ms.
Spatial and temporal resolutions have increased with
newer scanners. Temporal resolution represents the time to
acquire a single image, and faster gantry rotation has improved this significantly. Faster temporal resolution allows
for adequate imaging at higher heart rates and may reduce
the need for medications to slow the heart rate. Spatial
resolution (in voxels) describes the 3-dimensional image
size in any reconstruction plane, which has improved as
detectors have become smaller. The best spatial resolution
available with 16-slice scanners was 0.5 × 0.5 × 0.6 mm,
which improved on 64-slice scanners to 0.4 × 0.4 × 0.4 mm.
These voxels are referred to as isometric, which means they
are equal in all planes within the 3-dimensional dataset. By
comparison, the standard 2-dimensional spatial resolution
of ICA is 0.2 × 0.2 mm [9].
CCTA requires the use of iodinated contrast media, usually administered through an upper extremity intravenous
line at 4 to 6 mL/second. Some form of a timing mechanism
is used to determine at what time to begin scanning after
448 JCOM August 2007 Vol. 14, No. 8
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clinical review
the start of contrast administration. This most commonly
takes the form of a small timing bolus, with 15 mL of contrast administered while images are taken through the
aortic root to determine the time to peak enhancement, so
that optimum enhancement of the coronary arteries can
be achieved. This is particularly important in case of left
ventricular dysfunction. Sublingual nitroglycerin is given
to dilate the coronary arteries a few minutes prior to the
CCTA acquisition, helping to differentiate between normal
and diseased segments. Patients with a heart rate over
65 bpm usually receive oral and/or intravenous b blockers
prior to CCTA to reduce the heart rate. When the heart rate
is over 65 bpm, temporal resolution is inadequate and the
images are limited due to motion artifact. Patients who cannot receive b blockers may receive a calcium channel blocker
instead. With 64-slice CT scanners, the CCTA acquisition
itself requires as few as 5 seconds [10].
After the CCTA has been acquired, the dataset is reconstructed on the CT scanner in both end-diastole, the most
motion-free part of the cardiac cycle, and end-systole, the next
most motion-free part of the cardiac cycle. The 3-dimensional
data are reviewed on a workstation so that each coronary
artery can be viewed in its short and long axes, navigating
the dataset interactively to view each coronary segment in the
best plane for that segment.
More recently, dual-source CCTA has been introduced.
This combines two 32-detector arrays and 2 x-ray tubes
arranged at 90-degree angles to each other. Therefore, for
each 90-degree rotation of the gantry, 180 degrees of image
data are collected, resulting in a higher temporal resolution
and potentially improved image quality with less motion
artifacts. In a preliminary study of dual-source CCTA by
Achenbach et al [11] in 14 patients in which no medications
were used to control heart rate, 222 of 226 coronary artery
segments were free of motion artifacts despite a mean heart
rate of 71 bpm and a range from 56 to 90 bpm. It has been
suggested that dual-source CT allows motion-free CCTA
in patients with a heart rate greater than 65 bpm, but more
study is needed to substantiate this.
Risks of CCTA
The use of intravenous contrast can be associated with allergic reactions and renal failure. Many protocols exclude
patients with renal insufficiency to minimize these risks.
There is a significant radiation exposure with CCTA. The
effective radiation dose, expressed in millisieverts (mSv),
describes the overall risk when accounting for the various
involved organs. Younger patients may have a much higher
lifetime risk of developing radiation-associated malignancy
than older patients, which raises concerns for the use of
CCTA in low-risk young populations. Doses associated
with various exposures are described in Table 2. Radiation
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Table 1. Appropriate Indications for the Use of Coronary
Computed Tomography Angiography
Use
Indication
Evaluation of chest pain
syndromes
Intermediate pretest probability of
CAD and ECG uninterpretable or
unable to exercise
Uninterpretable or equivocal stress test
Evaluation of intracardiac structures
Evaluation of suspected coronary
anomalies
Acute chest pain
Intermediate pretest probability of
CAD and no ECG changes and serial enzymes negative
Asymptomatic detection
of CAD
None
Asymptomatic risk assessment
None
Preoperative evaluation
for noncardiac surgery
None
Morphology
Assessment of complex congenital
heart disease
Evaluation of coronary arteries in patients with new-onset heart failure
Suspected aortic or pulmonary disease
Evaluation of suspected aortic dissection, thoracic aortic aneurysm, or
pulmonary embolism
CAD = coronary artery disease; ECG = electrocardiogram. (Adaptclinical
review
ed from Hendel RC, Patel MR,
Kramer CM, et
al. ACCF/ACR/
SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic
resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology,
Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear
Cardiology, North American Society for Cardiac Imaging, Society
for Cardiovascular Angiography and Interventions, and Society of
Interventional Radiology. J Am Coll Cardiol 2006;48:1475–97.)
doses have increased with 64-slice scanners compared with
16-slice scanners, as the increasingly thinner slices require
higher radiation to maintain adequate signal-to-noise ratios.
In women, radiation dose to breast tissue during CCTA is a
concern; however, bismuth breast shields can be used to reduce this exposure. Radiation exposure with CCTA and ICA
has been projected to convey lifetime mortality risks of 0.07%
and 0.02%, respectively. When the other risks associated with
ICA are included, the overall lifetime mortality risks of CCTA
and ICA have been estimated at 0.07% and 0.13% [12].
There are methods to significantly reduce the radiation
dose, the most widespread of which is dose modulation
or ECG pulsing. During the part of the R-R interval when
data are not used to evaluate the coronary arteries, the mA
(milliampere) is reduced, ramping up at the part of the R-R
Vol. 14, No. 8 August 2007 JCOM 449
coronary ct angiography
Table 2. Radiation Dose Associated with Various Radiation Exposures
Exposure
Total Effective
Dose, mSv
Mean background radiation in 1 year (United States)
3.0
Two-view chest radiograph
0.08
Air travel per 1000 miles
Tc-99m sestamibi stress test
EBCT coronary calcium scoring
16-Slice CCTA without ECG pulsing
16-Slice CCTA with ECG pulsing
0.01
12.0–17.5
1.0–1.3
07.9–16.3
4.0–8.7
64-Slice CCTA without ECG pulsing
09.6–21.4
64-Slice CCTA with ECG pulsing
04.8–14.0
Invasive diagnostic coronary angiography
5.6
CCTA = coronary computed tomography angiography; EBCT =
electron-beam computed tomography; ECG = electrocardiogram;
mSv = millisieverts. (Adapted from Thompson RC, Cullom SJ.
Issues regarding radiation dosage of cardiac nuclear and radiography procedures [editorial]. J Nucl Cardiol 2006;13:19–23; and
Coles DR, Smail MA, Negus IS, et al. Comparison of radiation
doses from multislice computed tomography coronary angiography and conventional diagnostic angiography. J Am Coll Cardiol
2006;47:1840–5.)
interval used to visualize the coronary arteries. In 1 study,
ECG pulsing reduced the mean dose estimate of 64-slice
CCTA from 14.8 mSv to 9.4 mSv [13]. Newer techniques to
reduce doses include the use of prospective triggering, in
which data are only collected at a prospectively set part of the
R-R interval, with no radiation exposure during the rest of
the R-R interval; this has demonstrated promise with doses
as little as 1 to 3 mSv [14].
Accuracy
While early CCTA studies showed very good to excellent
sensitivity and specificity using 4-, 8-, and 16-detector CT
scanners, studies often excluded a substantial number of
patients, arteries, or segments from the analysis due to artifacts or insufficient contrast opacification of the coronary
arteries. A meta-analysis evaluated 28 studies using 4-, 8-,
or 16-slice CCTA compared with ICA as the reference standard. There were 617 patients enrolled in 4-slice CT studies,
50 patients in 8-slice studies, and 872 patients in 16-slice CT
studies. Data were pooled to provide average sensitivity and
specificity for detecting significant CAD, defined as greater
than 50% diameter stenosis. Using segment-based analysis,
average sensitivity was 83% with 4-slice scanners and 88%
with 16-slice scanners, and average specificity was 93% and
97%, respectively. With 4-slice CCTA, 78% of segments were
deemed adequate for evaluation, while 91% of segments
were evaluable with 16-slice CCTA. Since nonevaluable seg450 JCOM August 2007 Vol. 14, No. 8
ments were excluded from analysis, measures of accuracy
may be overestimated. Sensitivity was better in the proximal
and mid-artery segments, and lower in distal segments.
In addition, many studies excluded small vessel segments
with diameters less than 1.5 or 2.0 mm. Analysis by patient
resulted in an identical mean sensitivity of 95% and specificity of 84% for both 4- and 16-slice CCTA [15].
A more recent meta-analysis evaluated 47 studies that
compared CCTA and ICA in patients scheduled for ICA.
There were 20 studies that used 4-slice CCTA, 1 study with
8-slice CCTA, 19 studies with 16-slice CCTA, and 7 studies with 64-slice CCTA. Assessable segments with CCTA
increased significantly with 64-slice CCTA compared with
4- and 16-slice CCTA (p < 0.05), with pooled assessable
segments observed in 74% of segments with 4-slice CCTA,
92% of segments with 16-slice CCTA, and 97% of segments
with 64-slice CCTA. Pooled sensitivity and specificity for
the detection of CAD was 76% and 93% with 4-slice CCTA,
82% and 95% with 16-slice CCTA, and 92% and 94% with
64-slice CCTA, respectively. This suggests that 64-detector
CCTA has significant better diagnostic accuracy compared
with earlier scanners. The mean prevalence of significant
CAD in this study was 74%, indicating a very high pretest
probability of disease. The reliable exclusion of significant
CAD in these studies finds a high negative predictive
value in this population. While it is expected that the high
negative predictive value would also be present in low- or
intermediate-risk patient cohorts, it is also likely that the
positive predictive value would decrease [16].
Imaging Coronary Artery Stenosis with 64-Slice
CCTA
There are now many published studies that have compared
64-slice CCTA with ICA (Table 3), which generally find
excellent sensitivity and specificity for the detection of significant CAD (generally defined as a stenosis ≥ 50%). Patients
were recruited for CCTA from the pool of patients who were
already scheduled to undergo ICA. Hence, the prevalence of
significant disease is higher than it would be in a screening
population or a population of patients who may be undergoing other noninvasive tests such as stress echocardiography
or radionuclide imaging for suspected CAD.
It is important to note exclusions from these investigations. Many studies excluded segments, arteries, or patients
that were inadequately visualized on CCTA from the
subsequent analysis, which likely overestimates its accuracy. Smaller arteries, particularly those less than 1.5 mm
in diameter, are more difficult to visualize with CCTA than
the larger proximal segments. For this reason, some published studies have excluded all segments less than 1.5 mm
in diameter. For example, Leschka et al [19] excluded all
segments under 1.5 mm, but reported no nonanalyzable
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segments. Raff et al [28] did not exclude segments based on
size, but excluded 17% of segments from the segment-based
analysis because of inadequate visualization, predominantly due to either calcification or motion artifact. Leber et al
[18] excluded 4 of 59 patients from their analysis because of
inadequate studies. Patients with stents were included, but
13 segments with stents were excluded from the segmentbased analysis, and all patients with stents were excluded
from the patient-based analysis, resulting in the inclusion
of only 45 of 59 patients. This study stratified lesions by
stenosis severity. In the stent-based analysis, there was a
79% sensitivity for the detection of a stenosis less than 50%,
73% for a stenosis greater than 50%, and 80% for a stenosis
greater than 75%; specificity was reported as 97%. Analysis
by patient found a sensitivity of 88% for detecting a stenosis
greater than 50%, and an 85% specificity for excluding a
stenosis greater than 75%. IVUS was performed in 32 vessels
from 18 patients, with 46 of 55 plaques (84% sensitivity for
detection of any plaque) and 39 of 43 disease-free segments
correctly identified on CCTA (91% specificity). Compared
with IVUS, CCTA significantly underestimated lesion stenosis (50.4% vs. 41.1%; p < 0.001). CCTA also overestimated
the lumen area and underestimated the plaque area, which
was attributed to partial volume effects at the lumen-plaque
border secondary to overlapping attenuation values [18].
Fine et al [33] compared 66 patients undergoing CCTA
and ICA, and after excluding segments smaller than 1.5 mm
reported uninterpretable CCTA studies in 6% of patients.
After these were also excluded, analysis by artery yielded
95% sensitivity, 96% specificity, 97% positive predictive
value, and 92% negative predictive value for identifying stenosis greater than 50% [33]. Muhlenbruch et al [23] defined
significant stenosis as at least 70% and had a lower patientbased specificity and negative predictive value than studies
that used a 50% cutoff.
Calcification is known to contribute to both overestimation of stenosis and nonanalyzable segments. For example, Ong et al [25] reported that more segments were
interpretable with a lower calcium score (94% vs. 87%) in a
comparison of CCTA and ICA in which 68 patients had an
Agatston score equivalent of less than 142, and 66 patients
had a higher score. Raff et al [28] also compared the diagnostic accuracy of CCTA in patients stratified by calcium
score. Patient-based sensitivity and specificity for a low
score (Agatston score up to 100) were 94% and 95%, for a
moderate score (101–400) were 100% and 88%, and for a high
score (> 401) were 93% and 67%, respectively. This suggests a
significantly decreased specificity with increased coronary
artery calcification [28].
For this reason, some have suggested that a calcium score
threshold should be used above which CCTA is less useful.
However, other variables, such as the size and distribution
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of calcified plaques, should be considered. A calcium score
of 400 could mean many tiny calcified plaques or fewer larger plaques, the latter creating more of a challenge to CCTA
accuracy than the former. If calcium scoring is being done
as part of a CCTA examination, it is also not operationally
practical to process the examination data and generate the
calcium score before deciding to do the CCTA acquisition.
Evaluation of Coronary Stents
The evaluation of in-stent stenosis is challenging, as metal
causes variable degrees of blooming artifact (Figure 3).
There is a significant variability in the ability of CCTA to
evaluate in-stent restenosis, which may related to variables
such as stent type, size, and composition, scan protocol, and
the positional relationship of the stent to the scanner axis.
For example, in an in vitro comparison of 68 different stents
with 64-slice CCTA, in which all the stents were placed in
the same orientation and imaged perpendicular to the stent
axis, the visible lumen diameter ranged from 3% to 73% even
when using a sharp reconstruction algorithm and a highresolution dedicated kernel. In this study, 58 of the 68 stents
had a lumen visibility of at least 50%, while only 10 stents
had a lumen visibility of at least 66% [34]. This confirms not
only the difficulty of evaluating the coronary artery lumen
within stented segments but also in comparing studies of
clinical
populations with different types
of stents. Inreview
another study,
64-slice CCTA was used to evaluate in-stent dimensions of 4
different stents expanded to 3.0 mm diameter in vitro, with
IVUS as the reference standard. While the IVUS-measured
diameter ranged from 2.8 to 3.0 mm, the diameter measured
on CCTA ranged from 1.7 to 1.9 mm, with CCTA underestimating in-stent lumen diameter for all stent types [35].
Several studies of 64-detector CCTA have included patients with stents. Leber et al [18] excluded segments and
patients with stents from the primary analyses and reported
an analysis of the 13 stented segments separately. Only 7 of
the stents were correctly evaluated by CCTA; 2 of 4 stents
with restenosis were correctly identified, while 4 of 9 stents
without restenosis were reported as having restenosis.
Other studies have included segments with stents in the
primary analyses (Table 3). Schuijf et al [32] evaluated 61 patients with stents in 44 segments, reporting that all 3 in-stent
stenoses and all 41 stents without significant stenosis were
correctly identified. The study by Ehara et al [30] included
a subanalysis of 67 stents in 39 patients. After excluding 9
stents with poor image quality, they reported a sensitivity,
specificity, positive predictive value, and negative predictive
value of 93%, 96%, 87%, and 98%, respectively. Nikolaou et al
[31] included 15 patients with a total of 24 stents, of which
22 were interpretable with CCTA. Of these 22, CCTA made
the correct diagnosis of significant stenosis in 11 stents, with
1 false-negative and 10 false-positive CCTA results. When
Vol. 14, No. 8 August 2007 JCOM 451
coronary ct angiography
Table 3. Summary of Studies Comparing 64-Slice CCTA with ICA for the Detection of Significant Coronary Disease
Study
n
CAD
Prevalance,
%
Ghostine et al [17]
66
Leber et al [18]
59
Leschka et al [19]
67
Meijboom et al [20]
Meijboom et al [21]
Analysis per Segment
Excluded,
%
n
Sensitivity,
%
Specificity,
%
PPV,
%
NPV,
%
44
0
990
72
99
91
97
64
798
73
—
—
—
70
*7*
†0†
10050
94
97
87
99
70
26
0
10030
94
98
65
100
1040
85
0
15250
92
91
60
99
52
75
2
725
99
95
76
99
51
88
3
726
87
95
75
98
Oncel et al [24]
80
78
0
12000
96
98
91
99
Ong et al [25]
68
57
6
700
85
98
77
99
Ong et al [25]
66
89
130
631
80
93
79
94
Pugliese et al [26]
35
71
0
494
99
96
78
99
Pundziute et al [27]
60
53
—
—
—
—
—
—
Raff et al [28]
70
57
935
86
95
66
98
Ropers et al [29]
84
32
12
††4†
10830
93
97
56
1000
95
Mollett et al [22]
Muhlenbruch et al‡ [23]
Studies that include segments and patients with stents
Ehara et al [30]
69
88
8
884
90
94
89
Nikolaou et al [31]
72
57
100
923
82
—
—
—
Schuijf et al [32]
61
52
3
842
85
98
82
99
CAD = coronary artery disease; CCTA = coronary computed tomography angiography; ICA = invasive coronary angiography; NPV = negative predictive value; PPV= positive predictive value.
*In addition, segments and patients with stents were excluded from the analysis.
†In addition, any segments < 1.5 mm were excluded from further analysis.
‡Muhlenbruch et al defines significant stenosis as > 70%.
these stents were assessed for patency only, the correct diagnosis was made in 20 of 22 stents.
In a study of left main stent patency on 16- and 64-slice
CCTA, 70 of 74 patients had adequate scans, from which
CCTA correctly identified all 10 patients with in-stent restenosis, with false-positive results in 5 patients. In the 50
patients with quantitative IVUS and CCTA data, there was
good correlation between IVUS and CCTA in the assessment of stent diameter (r = 0.78) [36].
Evaluation of Bypass Grafts
Many studies have evaluated graft patency and distal graft
anastomoses with CCTA (Figure 4). For example, in a study
by Anders et al [37] using 16-slice CCTA to evaluate 32 patients with 94 bypass grafts, the sensitivity was 100% and
specificity was 98% for identifying a stenosis of 50% or more
among the interpretable grafts. However, many grafts were
uninterpretable; when all patients with at least 1 uninterpretable graft or anastomosis were included in the analysis,
only 25% could be excluded from having significant graft
452 JCOM August 2007 Vol. 14, No. 8
disease [37]. In a study of 16-slice CCTA by Chiurlia et al
[38] of 52 patients with 166 bypass grafts, only 1 graft was
excluded because of significant clip artifacts. The sensitivity
and specificity for detecting high-grade stenosis with CCTA
were 96% and 100%, respectively, and were both 100% for
detecting complete occlusion [38]. Schlosser et al [39] evaluated 48 patients with 131 bypass grafts using 16-detector
CCTA and reported that while the sensitivity and specificity for graft patency were 96% and 95%, only 74% of distal
anastomoses could be visualized. When the analysis was
done with the nonvisualized distal anastamoses assumed
stenotic, the sensitivity remained at 96%, but the specificity
decreased to 68%.
Another study examined 52 patients with 45 arterial and
64 venous bypass grafts undergoing scheduled ICA with
64-slice CCTA. The presence or absence of significant CAD
was correctly identified in all arterial grafts (10 had significant stenosis). For the vein grafts, CCTA correctly identified
all 39 with significant stenosis, and 24 of 25 without significant stenosis. This resulted in an overall sensitivity of 100%
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Table 3. continued
Analysis per Patient
Excluded,
%
n
Sensitivity,
%
Specificity,
%
PPV,
%
NPV,
%
97
0
66
97
95
93
*8*
†0†
45
88
—
—
—
67
1000
1000
1000
100
0
70
1000
92
82
100
0
1040
1000
75
96
100
2
51
1000
92
97
100
0
51
98
50
94
075
0
80
1000
1000
1000
100
—
—
—
—
—
—
—
—
—
—
—
—
0
35
1000
90
96
1000
0
60
91
96
97
90
0
†4†
70
95
90
93
93
81
96
91
83
98
3
67
98
86
98
86
6
68
97
79
86
96
2
60
94
97
97
93
Figure 3. Stent in the right coronary artery with coronary
computed tomography angiography (arrow). Note the difficulty assessing the lumen inside the stent for in-stent stenosis.
clinical review
and a specificity of 98% for the detection of significant graft
disease [40]. Another study retrospectively compared 31
patients with a total of 23 arterial bypasses and 73 venous
bypasses undergoing ICA with 64-slice CCTA. ICA was not
able to evaluate 1 arterial graft and 2 venous grafts, both of
which were well-visualized by CCTA but not included in
the analysis given the missing reference standard. The distal
anastamoses were not well visualized with CCTA in 3 of the
51 patent grafts and classified as stenotic for the analysis.
Of the 22 arterial grafts seen with ICA, 5 of 6 were correctly
identified with significant stenosis using CCTA, and 12 of
16 were correctly identified without significant stenosis.
Of the 71 venous grafts visualized with ICA, all 40 grafts
with significant stenosis were correctly identified, while 30
of 31 without significant stenosis were correctly identified.
Analysis by patient found 100% sensitivity with CCTA in
detecting the 24 patients with significant stenosis, and 5
of the 7 patients without significant disease were correctly
identified [41].
Ropers et al [42] used 64-detector CCTA in 50 patients
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Figure 4. This volume-rendered image demonstrates 2 patent saphenous vein grafts (arrows). A patent left internal
mammary artery is also seen (arrowheads).
with 138 grafts, including only segments and grafts larger
than 1.5 mm in diameter. All grafts were correctly identified
as patent or occluded. Among patent grafts, the sensitivity
and specificity for the detection for a stenosis of at least 50%
were 100% and 94%, respectively.
CCTA in the Emergency Department
The high negative predictive value of CCTA has led to
considerable interest in using CCTA in the emergency department setting as a possible way to safely discharge home
Vol. 14, No. 8 August 2007 JCOM 453
coronary ct angiography
the majority of chest pain patients who are not having an
ACS, saving time and cost. This interest has been fueled by
several recent studies. Hoffman et al [43] performed 64-slice
CCTA in 103 patients with acute chest pain and suspected
ACS who had a negative initial ECG and cardiac markers.
These patients had CCTA in addition to usual care, and the
CCTA results were not revealed at the time of the initial
emergency department visit. Fourteen of the 103 patients
had a confirmed ACS based on standard clinical care with
serial ECGs, cardiac markers, and stress testing or cardiac
catheterization in most patients. CCTA correctly excluded
an ACS in all patients based on the absence of significant
stenosis or plaque. The absence of a significant stenosis
predicted the absence of an ACS with a sensitivity of 100%,
specificity of 82%, positive predictive value of 46%, and
most importantly a negative predictive value of 100%.
Goldstein et al [44] performed a randomized clinical
trial of usual care (including stress nuclear perfusion scintigraphy) versus 64-slice CCTA in 197 low-risk emergency
department patients with chest pain and negative ECGs
and cardiac enzymes after 4 hours. Among the 461 patients
screened, 10% declined consent, and 46% were excluded
from the study predominantly because of pulmonary disease that precluded the use of b blockers, potential contrast
allergy, known CAD, or atrial fibrillation. Of the 99 patients
in the CCTA arm, 67 had normal coronary arteries or a
stenosis of 25% or less and a calcium score of less than 100
Agatston units and were eligible for immediate discharge
home. Eight patients with greater than 70% stenosis on
CCTA were referred for ICA, and 24 patients were sent for
a nuclear stress test either because they did not fit into the 2
aforementioned groups or at least 1 major coronary segment
was not interpretable. Compared with the usual care group,
patients in the CCTA arm had a significantly lower time to
establish or exclude significant CAD (3.4 vs. 15 hours; p <
0.001) and lower cost of care ($1586 vs. $1872; p < 0.001). After
6 months of follow-up, there were no cases of ACS or death
in either group, although this study was underpowered to
detect a difference in coronary event rates [44].
Lastly, Gallagher et al [45] compared nuclear stress
testing and CCTA in 92 low-risk patients presenting to the
emergency department with chest pain. Patients with stenosis greater than 50% on CCTA, a calcium score greater than
400, or a reversible perfusion defect on nuclear stress testing
were considered for ICA. After 7 patients were excluded
for an uninterpretable CCTA in at least 1 major segment,
CCTA was not significantly more or less accurate than
nuclear stress testing in the detection of an ACS, significant
CAD stenosis on catheterization, or an adverse event within
30 days (CCTA sensitivity, 86% and specificity, 92%; nuclear
stress sensitivity, 71% and specificity, 90%). However, the
confidence intervals around these test characteristics were
454 JCOM August 2007 Vol. 14, No. 8
very wide, due to the small number of cardiac events. For
the 66 patients with both a negative CCTA and a negative
perfusion study, the negative predictive value of the combined test combination was 100%, whereas for the 6 patients
with a positive CCTA and positive perfusion study, only 4
of 6 had a confirmed ACS [45]. Obvious limitations for this
study are the lack of ICA in all patients with abnormal noninvasive testing and the lack of power to detect significant
outcome differences in this low-risk population.
Limitations of Current CCTA Studies
There are several limitations in the literature currently
available to evaluate CCTA. Although there are now many
published single-center studies that show excellent diagnostic accuracy for the detection of significant CAD, the studied
populations in each series have been small. In all studies
evaluating the accuracy of CCTA in which ICA has been
used as the reference standard, the prevalence of disease
has been very high, as patients were recruited from those
already scheduled to undergo ICA for clinical reasons.
There are no studies of how CCTA performs in populations
with a lower prevalence of disease, such as the population
of patients that undergo myocardial perfusion scintigraphy
for suspected CAD or asymptomatic high-risk screening
populations, which may alter the high sensitivities and
specificities reported to date. In addition, current studies
frequently use readers with extensive experience in cardiac
imaging, and the reported results often represent a consensus of readers.
It is unclear how CCTA compares with other noninvasive tests for CAD, such as exercise treadmill tests, stress
echocardiography, or myocardial perfusion scintigraphy.
For example, a recent study found that 64-slice CCTA lesions did not predict perfusion deficits on gated-SPECT
[46]. Although most CCTA studies define significant lesions
as those with at least 50% stenosis, severe reductions in
coronary flow reserve typically occur at a stenosis of 70%
or greater, emphasizing that CCTA cannot predict the functional relevance of detected CAD.
CCTA appears to be accurate for detecting bypass graft
patency but not for evaluating distal anastomoses. Caution
should be used when evaluating stents, as there is great variability in the accuracy of evaluating in-stent restenosis.
Conclusion
CCTA provides noninvasive imaging of the coronary arteries,
which may be an alternative for ICA in some patients. CCTA
has a high sensitivity and specificity in for detection of significant CAD, and newer scanners have resulted in improved
temporal and spatial resolution as well as fewer poorly visualized segments. CCTA has potential advantages over ICA with
its noninvasive nature and its ability to visualize the plaque
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clinical review
and wall in addition to the lumen visible with ICA, although
ICA still has higher spatial resolution, is associated with less
radiation exposure, and is better able to quantify stenosis.
The use of CCTA in low-risk patients with chest pain has
great promise for rapid patient triage as well as decreasing
health care costs. Additional studies are needed to determine
the best roles for CCTA in the evaluation of patients with
chest pain.
8.
9.
10.
Corresponding author: Ella A. Kazerooni, MD, MS, Taubman Ctr.,
Rm. 2910K, 1500 E. Medical Center Dr., Ann Arbor, MI 48109.
Financial disclosures: None.
11.
Author contributions: conception and design, TL, MM, EAK; analysis and interpretation of data, TL, MM, EAK; drafting of the article,
TL, MM, EAK; critical revision of the article, TL, MM, EAK.
12.
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456 JCOM August 2007 Vol. 14, No. 8
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